Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: A multiple regression analysis

There is considerable evidence that stress-related psychiatric disorders, including depression and post-traumatic stress disorder (PTSD), are associated with hypersecretion of corticotropin-releasing factor (CRF) within the centralnervous system (CNS). One line of evidencethat is consistent with centralCRFhypersecretion in these disorders is the blunted adrenocorticotropin hormone (ACTH) response tointravenous CRF administration, likely a consequence, at least in part, of downregulation of anterior pituitary CRF receptors. The presentstudy tests the hypothesis that elevated cerebrospinal fluid (CSF) concentrations of CRF and a secondary ACTH secretagogue, argininevasopressin (AVP), are associated with diminished adenohypophysealresponses in a standard CRF stimulation test. CSF concentrationsof CRF and AVP, and plasma ACTH responses to the administration of 1 mg/kg ovine CRF (oCRF) were measured in healthy adultwomen with and without current major depression and/or a history of significant childhood abuse. The primary outcome measure wasACTH area underthe curve (AUC) in the CRF stimulation test. Multiple linear regression was performed to identify the impact of CSFCRF and AVP concentrations upon the pituitary response to CRF stimulation. The regression modelexplained 56.5% of the variation inthe ACTH response to CRF stimulation. The relationship of CSF concentrations of CRF to ACTH responses to CRF were best describedby a third-order function that was inversely correlated over most of the range of studied values. The association of ACTH response withCSF concentration of AVP and the dose of oCRF followed second-order kinetics. These findings support the hypothesis that centralCRFhypersecretion is associated with a blunted ACTH response to exogenously administered CRF, explaining almost 60% ofthe variation inthe ACTH response to CRF.